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Award Ceremony Speech

Presentation Speech by Professor F.
Henschen, member of the Staff of Professors of the Royal Caroline Institute,
on December 10, 1928

Your Majesty, Your Royal Highnesses, Ladies
and Gentlemen.

In awarding the 1928 Nobel Prize for Medicine to Dr. Charles
Nicolle, Director of the Pasteur Institute at Tunis, the Caroline
Institute wished to pay tribute to a man who has realized one of
the greatest conquests in the field of prophylactic medicine,
i.e. the vanquishing of typhus.

Typhus is an acute infectious disease which, by its clinical
evolution, its contagiousness and the conditions under which
immunity is conferred shows considerable resemblance to ordinary
measles. In severe cases, a state of stupor or even deep coma may
occur. On account of the rash it causes the disease has been
called exanthematous typhus; it has nothing in common, however,
with what is properly called typhoid, i.e. enteric fever. In
certain epidemics, particularly where children are concerned,
epidemic typhus takes a relatively benign form; in adults,
however, and if conditions are unfavourable, the mortality rate
can reach the frightening proportion of between 50 and 60%.

The epidemiology of typhus presents a number of characteristics
which, understandably, appeared most mysterious to physicians of
past ages. It seemed, in fact, impossible to protect oneself
against this disease which claimed many victims, even in the
medical profession itself.

The general opinion used to be that typhus was transmitted more
or less in the same way as measles or influenza, i.e. by direct
contact, by dust, or by what is known as «droplet»
infection. Around 1880 and 1890 when the part played by insects
as carriers of infection was established, various people began to
suspect that typhus could well be transmitted in the same way, in
particular by parasites affecting man. This hypothesis, however,
excited no special interest. The way in which the disease was
actually disseminated was unknown and remained so, and there
were, therefore, no effective measures available to combat the
disease.

One of the peculiarities of typhus is the way in which it tends
to cause serious epidemics, flaring up suddenly and coinciding
with the previous occurrence of some serious public calamity.
Populations in the throes of war or famine fell victim to the
disease, which caused numerous deaths, sometimes as many as
hundreds of thousands. Thus originated certain expressive
synonyms, such as «camp typhus», «famine
typhus», «jail typhus» by which the disease has
sometimes been known. As one author so truly says, the history of
typhus is the history of human misfortune.

The disease has been known since the beginning of all time. The
plague which devastated Attica, especially Athens in the year 430
B.C., and which Thucydides describes in his work on the
Peloponnesian War, was most likely an epidemic of typhus. The
picture that the great historian draws of the disease agrees in
certain respects, down to the smallest details, with the clinical
picture we were able to observe during the Great War. Epidemics
followed one another without respite during the great wars of the
sixteenth and seventeenth centuries. At the end of the Thirty
Years' War, typhus raged over the whole of Central Europe. The
Napoleonic Wars caused the disease to flare up again. In the
general disorganization which followed the Grand Army's retreat
from Russia, typhus claimed innumerable victims amongst the
troops and amongst the civilian population. Further epidemics
broke out during the Crimean War and the Russo-Turkish War,
affecting both sides.

With the progress of civilization and during the period of peace
and prosperity which, in all, lasted from the end of the
nineteenth century until 1914, typhus seemed of its own accord to
have become restricted to certain remote regions of Europe and to
certain extra-European countries where, from time immemorial, the
disease had existed endemically.

At the beginning of this North Africa was among these
non-European countries where the disease had been a veritable
national scourge for several centuries. As soon as he took up his
appointment as Director of the Pasteur Institute at Tunis, young
Dr. Charles Nicolle was immediately brought into contact with the
scientific and practical problems that typhus had created in this
country. As soon as he took up his post, Nicolle immediately with
extraordinary energy attacked these problems. He visited patients
in their own homes, examining their beds and their sordid rags,
whilst undertaking at the same time a strict enquiry within the
hospitals. This work was to cost the life of two of his
collaborators. He was led to an observation which could hardly
have escaped the attention of earlier workers, i.e. that whilst
typhus patients continued to spread infection up to the point
when they entered the hospital waiting-room and amongst those who
took charge of their clothing, they became completely inoffensive
as soon as they had been bathed and dressed in the hospital
uniform. At this point they could be admitted to the general
wards without the slightest risk. Nicolle concluded that the
pathogenic agent must necessarily be related to one factor,
carried by the patient himself and transmissible to others, a
factor which no longer acted once the patient had bathed and
changed his clothing; this factor, therefore, could only be a
parasite, the body louse, which lives on the patient's body and
in his clothing. This simple observation contains in essence
Nicolle's discovery.

In order to further his research Nicolle now made experiments on
animals. Previously, some research workers had succeeded in
inoculating healthy individuals with typhus by injecting blood
from a patient, but all attempts to inoculate animals had failed
up till then. After several unsuccessful attempts, Nicolle
succeeded at the beginning of 1909 in inoculating chimpanzees
with typhus and, from the chimpanzee, he was able to inoculate
monkeys of a lower order by injection of blood. As early as
September of the same year Nicolle and his collaborators were
able to demonstrate that lice which had previously bitten
contaminated monkeys transmitted the infection to healthy animals
simply by biting them. The part played by the body louse as a
transmission agent had thus been proven experimentally.

The secrets of this terrible disease were then laid bare one
after another. The first problem was to define the conditions
under which infection by the body louse took place. It was
possible to establish that the blood of a typhus patient could
transmit infection from some hours before the appearance of fever
until the first days of recovery. The insect could therefore
absorb the pathogenic agent during the whole course of the
disease, even before the disease became apparent and after the
fever had disappeared.

The parasite's bite is not however immediately dangerous; it only
becomes virulent after about a week when the pathogenic agent has
had time to multiply in the parasite's digestive tube. Contagion
is also possible by means other than the parasite's bite: it is
sufficient that the skin and clothing be soiled by the excreta of
an infected parasite and that the patient infect himself by
scratching, for the disease to develop. This form of transmission
most probably plays at least as important a role as the direct
bite.

Nicolle was not long in making another important discovery: he
established that the germ of typhus is not transmitted to new
generations of parasites. The epidemic dies out of its own accord
when the contaminated adult insects die. All these observations
are obviously of the greatest importance from the point of view
of combating the disease.

Nicolle and his collaborators had established at an early stage
of their researches that monkeys who had recovered from a first
attack of the disease became resistant to further contamination.
This observation led them to a series of important discoveries
concerning the conditions necessary for immunization against
typhus, and led to a series of successful attempts to exert
preventive and attenuating effects on the disease with serum
taken from convalescents and by vaccination.

Nicolle's discovery that it is possible to inoculate the guinea
pig with typhus was an important step forward in the study of
this disease. By successive inoculations from one animal to
another, it became possible to preserve the agent of typhus in
the laboratory for an unlimited period; it has not yet been
possible to cultivate the virus on artificial substrates, and our
knowledge of its morphology and biology is still extremely
limited.

The study of typhus in the guinea pig led Nicolle to another very
important discovery: certain infected animals may be germ
carriers even though they present no apparent symptoms. Not even
a slight fever indicates that they are contagious. This form of
the disease had been hitherto unknown. Nicolle calls this form of
typhus «inapparent» typhus and considers it to be the
prototype of a group of latent infectious diseases of the same
type. Nicolle's discovery of the inapparent infection orientated
the work of scientists towards a hitherto unexplored field of
research. These new concepts are highly significant, even as
regards direct action against infectious diseases.

It soon became apparent that the discovery of the part played by
the body louse in the transmission of typhus was of the greatest
practical importance: it now became possible to combat the
terrible disease by rational methods. In fact, within two years
Nicolle and his collaborators succeeded in ridding Tunis entirely
of a disease which had raged there each winter from time
immemorial.

But in 1910 who would have guessed that the results of Nicolle's
research were about to be put to practical use on a vast
scale?

When the Great War broke out and many Russian and Serbian
prisoners were interned in German and Austrian prison camps,
typhus, which until then had hardly attracted the attention of
European doctors at all, was not long in making an appearance. In
spite of the precautions ordinarily taken against epidemics, it
was quickly transmitted from one man to another, from home to
home, regardless of age and in defiance of all the laws of
epidemiology. The armies were threatened with a veritable
catastrophe. The epidemic broke out in the same way amongst the
civilian population in regions of the eastern front devastated by
war. The Balkan Peninsula was affected badly, but the disease
spared no part along the whole front, from Finland to
Mesopotamia. The value of Nicolle's discovery was once again made
apparent. The Great War provided the opportunity for a
clinico-experimental application of Nicolle's work on a large
scale. As a French doctor said, one had to see the deserted
Serbian towns to realize the desolation that can be caused by
typhus, the satellite of war; one had to see for oneself the
resurrection of whole areas, entirely due to the hygienic
measures developed from Nicolle's discoveries, to appreciate
fully the significance of these discoveries. Remembering the
great losses incurred through another wartime epidemic, Spanish
influenza, a far less serious disease in itself, one shudders to
think of what might have happened in the Great War if we had been
unable to combat typhus successfully.

Indubitably, the nature has not changed and we still know of no
effective therapeutic action against this disease. Nevertheless,
this terrible plague has become a mere contagious disease and is
no longer considered in terms of devastating epidemics. Thanks
mainly to the work of Charles Nicolle, we have now completely
mastered the disease. The man who has vanquished typhus deserves
the gratitude of the whole human race.

In the absence of Mr. Nicolle, the honour of whose presence is
denied us today, I ask your Excellence, in your quality of
Minister representing the French Republic, to accept on his
behalf and to convey to him the prize and diploma. May I also ask
you to convey to your illustrious compatriot the tribute and
sincere congratulations of the Caroline Institute.